Copeptin in autosomal dominant polycystic kidney disease: real-world experiences from a large prospective cohort study

Lay Summary Autosomal-dominant polycystic kidney disease (ADPKD) is a genetic condition that can cause kidney damage. Researchers have been looking for new ways to predict how the disease will progress, so that patients can be offered the best treatment options. Copeptin is a substance that has been identified as a possible new marker for ADPKD. In this study, researchers measured copeptin levels in the blood of tolvaptan-naive ADPKD patients and ADPKD patients taking tolvaptan, a medication that can slow the progression of the disease. They found that copeptin levels were linked to kidney function and could help predict how the disease would progress in the future. The study also showed that tolvaptan increased copeptin levels. This research could help doctors make better treatment decisions for ADPKD patients. Background The identification of new biomarkers in autosomal-dominant polycystic kidney disease (ADPKD) is crucial to improve and simplify prognostic assessment as a basis for patient selection for targeted therapies. Post hoc analyses of the TEMPO 3:4 study indicated that copeptin could be one of those biomarkers. Methods Copeptin was tested in serum samples from patients of the AD(H)PKD study. Serum copeptin levels were measured using a time-resolved amplified cryptate emission (TRACE)-based assay. In total, we collected 711 values from 389 patients without tolvaptan treatment and a total of 243 values (of which 64 were pre-tolvaptan) from 94 patients on tolvaptan. These were associated with rapid progression and disease-causing gene variants and their predictive capacity tested and compared with the Mayo Classification. Results As expected, copeptin levels showed a significant negative correlation with estimated glomerular filtration rate (eGFR). Measurements on tolvaptan showed significantly higher copeptin levels (9.871 pmol/L vs 23.90 pmol/L at 90/30 mg; P < .0001) in all chronic kidney disease stages. Linear regression models (n = 133) show that copeptin is an independent predictor of eGFR slope. A clinical model (including eGFR, age, gender, copeptin) was nearly as good (R-2 = 0.1196) as our optimal model (including height-adjusted total kidney volume, eGFR, copeptin, R-2 = 0.1256). Adding copeptin to the Mayo model improved future eGFR estimation. Conclusion Copeptin levels are associated with kidney function and independently explained future eGFR slopes. As expected, treatment with tolvaptan strongly increases copeptin levels.